This proposal seeks funding for an NRSA Institutional Predoctoral Training Grant from the Systems and Integrative Biology Program of the National Institute for General Medical Sciences. This grant will support predoctoral training in Redox Biology and Medicine (RBM) leading to a Ph.D. degree at Wake Forest University. The RBM Training Program is a multi-disciplinary, multi-departmental program that has as its goal the training of researchers working at the interface of biomedical sciences, biology, chemistry and physics to communicate and work across disciplines to delve into the specialized chemistry of oxidation and reduction which directs signal transduction pathways and modulates disease. The 24 members of the RBM training faculty are highly collaborative, and include faculty from Biochemistry, Molecular Medicine, Cancer Biology, Biomedical Engineering, Chemistry, Biology, and Physics. Major scientific themes of the RBM Training Program include the overlapping areas of (i) oxidative modifications regulating signal transduction pathways, (ii) redox regulation of nucleic acid metabolism and cell cycle, (iii) reactive nitrogen species biochemistry and biophysics relating to human health, and (iv) redox-linked mechanisms of disease initiation, progression and treatment. The RBM training program has a flexible curriculum built around a common core of a course in Fundamentals in Redox Biology and Medicine and technology-specific minicourses, as well as the discipline- specific courses to meet the requirements of the Ph.D. programs of the trainees. Students in the program are trained in such areas as chemical biology, proteomics and metabolomics, enzymology, animal models of disease, mitochondrial biology and network modeling. The training program takes advantage of the activities initiated by the Center for Molecular Signaling synergistically with the Center for Redox Biology and Medicine, including a well-developed system of interdisciplinary seminars and retreats to promote interaction among members of the program. Students also participate in trainee-focused chalk talks which foster development in the cross-discipline communication skills so critical to the multi-disciplinary research in this field. We also offer specific training in skills for a wide variety of potential careers for our Ph.D. graduates, including academic careers, careers in the biotechnology and pharmaceutical industries, as well as careers in the intellectual property arena. We have developed a pipeline in which Master's degree students in Biomedical Science, Chemistry, Physics, Mathematics and Computer Science can transition into Ph.D. training in our program. Funding is requested for 4 predoctoral positions out of the steady state level of 20-30 students in the laboratories of the training faculty. These positions will be used to support students in the second year or beyond, at which time it will be apparent that their dissertation research is consistent with the goals of the Program. Support will be for a maximum of two years, after which the students will be supported by the research funding of their advisors or their own individual fellowships.